Proprietary targeting of Oligonucleotide to vulnerable splicing events to efficiently silence genes

Overview
The principle of antisense technology is the sequence-specific binding of an antisense oligonucleotide (ASO) to target mRNA and prevent gene translation. We have found the individual events that are most vulnerable to disruption in cancer cells and developed a method to target these events. We can further restrict the points of vulnerability to genes that are presumably more important to cancer cells than to the healthy cells of origin.

Market Opportunity

There are 20 million new cancer cases and 10 million deaths from cancer globally every year. ASOs have recently shown great promise as therapeutic agents, with at least nine approved by the FDA. Nearly 200 clinical trials of ASO oncology drugs are ongoing, with more than 15 in Phase 2 or greater.

Innovation and Meaningful Advantages

Each gene is copied into a transcript (pre-mRNA), which then undergoes, on average, ten splicing events to create a protein-coding template (mRNA). Our research has shown us how to identify vulnerable splicing events, and we now hold proprietary information on anti-splicing oligonucleotide target identification.

We have discovered ASOs that potentially disrupt essential splicing events in cancer cells. Using panels of splicing reporters, we have determined that the ability of an exon to tolerate a mutation is inversely proportional to the strength of its neighboring splice sites. These hotspot exons are more susceptible to splicing perturbation through drug treatment and knock-down of RNA-binding proteins.

Machine learning was used to identify more than 4,300 exons as vulnerable, and we are in the process of identifying additional exons that are vulnerable in cancer but not in non-cancerous cell types. We estimate that 1,400 exons in the human genome are hotspots.

Collaboration Opportunity

We are interested in exploring 1) startup opportunities with investors; 2) research collaborations with leading pharmaceutical companies to develop this method of treatment; and 3) licensing opportunities with companies.

Principal Investigator

William G. Fairbrother, PhD

Professor of Biology

Brown University

william_fairbrother@brown.edu

https://vivo.brown.edu/display/wfairbro

IP Information

Provisional Application Filed

Publication

Glidden DT, Buerer JL, Saueressig CF, Fairbrother WG. Hotspot exons are common targets of splicing perturbations. Nature Communications 2021 May 12;12:2756. doi.org/10.1038/s41467-021-22780-2.

Contact

Andrew Bond, PhD

Senior Director of Business Development

andrew_bond@brown.edu

Brown Tech ID 3035

Website

http://brown.technologypublisher.com/technology/48603

Contact Information

TTO Home Page: http://brown.technologypublisher.com

Name: Andrew Bond

Title: Director of Business Development – Life Sciences

Email: andrew_bond@brown.edu